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Abstract Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

Objectives: This study aimed to explore the effects of the mini-clinical evaluation exercise (mini-CEX) teaching model based on nurse-faculty collaboration in Fundamentals of Nursing course. Methods: A quasi-experimental design was conducted. A total of 111 nursing students of two parallel classes were recruited from a nursing college in Guilin, China from February to December 2022, and allocated to the intervention group (n = 56) and control group (n = 55). The intervention group received a mini-CEX teaching model based on nurse-faculty collaboration, the teaching-learning process included scenario creation (10 min), inquiry-based learning (30 min), case report (30 min), scenario simulation exercise (40 min), and effectiveness evaluation (10 min). While the control group received conventional teaching method. All students were invited to complete the College Classroom Climate Assessment Scale (CCCA) and the Chinese version of the Competency Inventory for Nursing Students (CINS-CV) before and after the intervention. Course achievement of students was evaluated. After the intervention, the intervention group was asked an open-ended question to explore the difficulties or challenges they had encountered. Results: After intervention, the CCCA score (208.36 ± 23.25 vs. 190.60 ± 28.83), CINS-CV score(106.95 ± 14.48 vs. 99.55 ± 14.60), the oretical exam score (83.01 ± 4.27 vs. 79.75 ± 5.45), and scenario simulation exam score (89.23 ± 3.17 vs. 81.42 ± 7.19) of intervention group were higher than those of the control group (P＜0.01). The open-ended questionnaire survey revealed that the difficulties or challenges faced by the intervention group were mainly related to case analysis, group cooperation, learning material acquisition, and teacher guidance. Conclusion: Applying the mini-CEX teaching model based on nurse-faculty collaboration could cultivate nursing students’ competency, build a positive classroom climate, and improve the course achievement of students.

Magnesium and its alloys are considered excellent materials for biodegradable implants because of their good biocompatibility and biodegradability as well as their mechanical properties. However, the rapid degradation rate severely limits their clinical applications. Plasma electrolytic oxidation (PEO), also known as micro-arc oxidation (MAO), is an effective surface modification technique. However, there are many pores and cracks on the coating surface under conventional PEO process. The corrosive products tend to penetrate deeply into the substrate, reducing its corrosion resistance and the biocompatibility, which makes PEO-coated Mg difficult to meet the long-term needs of in vivo implants. Hence, it is necessary to modify the PEO coating. This review discusses the formation mechanism and the influential parameters of PEO coatings on Mg. This is followed by a review of the latest research of the pretreatment and typical amelioration of PEO coating on biodegradable Mg alloys in the past 5 years, including calcium phosphate (Ca–P) coating, layered double hydroxide (LDH)-PEO coating, ZrO2 incorporated-PEO coating, antibacterial ingredients-PEO coating, drug-PEO coating, polymer-PEO composite coating, Plasma electrolytic fluorination (PEF) coating and self-healing coating. Meanwhile, the improvements of morphology, corrosion resistance, wear resistance, biocompatibility, antibacterial abilities, and drug loading abilities and the preparation methods of the modified PEO coatings are deeply discussed as well. Finally, the challenges and prospects of PEO coatings are discussed in detail for the purpose of promoting the clinical application of biodegradable Mg alloys.

Pard3 is a core component of the Par complex and is a critical regulator of cell polarity. However, the biological role of Pard3 in breast cancer (BC) remains unclear. In this study we found that Pard3 levels were down-regulated in BC cells and tissues. Pard3 down-regulation was associated with the TNM stage of BC. Further, Pard3 knockdown enhanced colony formation and metastasis in vitro and in vivo. Interestingly, Pard3 knockdown also enhanced Snail1 deubiquitination and promoted BC invasion and migration via Snail1. Moreover, Pard3 silencing led to activation of the NFκB pathway, promoting the expression of USP28. Subsequently, USP28 interacted with and deubiquitinated Snail1; these effects were dependent on GSK-3β-mediated phosphorylation. Together, the findings indicated that Pard3 knockdown facilitated the migration and invasion of BC cells by enhancing USP28-mediated Snail1 deubiquitination. Collectively, targeting the Pard3/NFκB/USP28/Snail1 signaling pathway might be a promising treatment option for breast cancer.

Cardiovascular disease remains the leading cause of death and morbidity worldwide. Inflammatory responses after percutaneous coronary intervention led to neoathrosclerosis and in-stent restenosis and thus increase the risk of adverse clinical outcomes. In this work, a metabolism reshaped surface is engineered, which combines the decreased glycolysis promoting, M2-like macrophage polarization, and rapid endothelialization property. Anionic heparin plays as a linker and mediates cationic SEMA4D and VEGF to graft electronically onto PLL surfaces. The system composed by anticoagulant heparin, immunoregulatory SEMA4D and angiogenic VEGF endows the scaffold with significant inhibition of platelets, fibrinogen and anti-thrombogenic properties, also noteworthy immunometabolism reprogram, anti-inflammation M2-like polarization and finally leading to rapid endothelializaiton performances. Our research indicates that the immunometabolism method can accurately reflect the immune state of modified surfaces. It is envisioned immunometabolism study will open an avenue to the surface engineering of vascular implants for better clinical outcomes.

Abstract Background Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-β1 (TGF-β1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling. Methods Female C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors. Results The expression of SCD1 was increased in fibroblasts exposed to TGF-β1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-β1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation. Conclusions The data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.

In this study, high-strength ceramic lightweight aggregates were prepared from oil-based drill cutting pyrolysis residues, and their formation mechanism and expansion during sintering were examined. It was found that the Al2O3 suppressed the melting process and increased the particle strength. In particular, Al atoms penetrated the liquid phase and formed a Si–Al–O crystal structure with four ligands, which reacted with CaO and BaO to produce aluminosilicate crystals, such as BaAl2Si2O8 and CaAl2Si2O8, which increased the compressive strength. Scanning electron microscope images revealed that the glass phase also contributed toward the high strength of ceramic materials by adhering to crystal grains and forming a concrete-like structure. Energy-dispersive X-ray spectroscopy data suggested that similar to Ca atoms, Ba atoms in pyrolysis residues played a critical role in the production of aluminosilicate, while transmission electron microscopy images confirmed that different phases were not well separated as Ba and Ca were stabilized in the same crystal grains. After SiC addition and increasing the sintering temperature, the product density significantly decreased while its porosity increased.

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Here, the authors identify differential innate immune responses induced by C. auris and Candida albicans in vitro and in vivo, which correlate with structural features of the cell wall.

Abstract Background Previous studies have indicated that chronic emotional stressors likely participate in the occurrence of cancers. However, direct evidence connecting stress and colorectal cancer development remains almost completely unexplored. Methods Chronic stress mouse model was used to investigate the influence of stress on tumorigenesis. Several major agonists and antagonists of adrenergic receptors were applied to investigate the effects of β-adrenergic signaling on the development of CRC. Chromatin immunoprecipitation assays (CHIP) were used to investigate the binding of p53 and CEBPB to TRIM2 promoter. Mammosphere cultures, Cell Counting Kit-8 (CCK-8) assay, colony-formation assay, scratch wound healing assays, qPCR, immunofluorescence, coimmunoprecipitation and western blotting were used to explore the effect of stress-induced epinephrine on the CEBPB/TRIM2/P53 axis and the progress of CRC cells. Results In this study, we found that stress-induced epinephrine (EPI) promotes the proliferation, metastasis and CSC generation of CRC primarily through the β2-adrenergic receptor. Furthermore, our studies also confirmed that chronic stress decreased the stability of p53 protein by promoting p53 ubiquitination. Results of transcriptome sequencing indicated that TRIM2 was overexpressed in cells treated with EPI. Further studies indicated that TRIM2 could regulate the stability of p53 protein by promoting p53 ubiquitination. Finally, we further proved that CEBPB was regulated by EPI and acts as the upstream transcription factor of TRIM2. Conclusions Our studies proved that stress-induced EPI promotes the development and stemness of CRC through the CEBPB/TRIM2/P53 axis.

The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.

Conoscopic interferometry is a promising detection technique for ultrafast acoustics. By focusing a probe beam through a birefringent crystal before passing it through a polarizer, conoscopic interferences sculpt the spatial profile of the beam. The use of these patterns for acoustic wave detection revealed a higher detection sensitivity over existing techniques, such as reflectometry and beam distortion detection. However, the physical origin of the increased sensitivity is unknown. In this work, we present a model, describing the sensitivity behavior of conoscopic interferometry with respect to the quarter-wave plate orientation and the diaphragm aperture, which is validated experimentally. Using the model, we optimize the detection sensitivity of conoscopic interferometry. We obtain a maximal sensitivity of detection when placing the diaphragm edge on the dark fringes of the conoscopic interference patterns. In the configurations studied in this work, conoscopic interferometry can be 18 dB more sensitive to acoustic waves than beam distortion detection.

Specialized transformers-based models (such as BioBERT and BioMegatron) are adapted for the biomedical domain based on publicly available biomedical corpora. As such, they have the potential to encode large-scale biological knowledge. We investigate the encoding and representation of biological knowledge in these models, and its potential utility to support inference in cancer precision medicine—namely, the interpretation of the clinical significance of genomic alterations. We compare the performance of different transformer baselines; we use probing to determine the consistency of encodings for distinct entities; and we use clustering methods to compare and contrast the internal properties of the embeddings for genes, variants, drugs, and diseases. We show that these models do indeed encode biological knowledge, although some of this is lost in fine-tuning for specific tasks. Finally, we analyze how the models behave with regard to biases and imbalances in the dataset.

Abstract Background Up-regulation of aerobic glycolysis has been reported as a characterization of asthma and facilitates airway inflammation. We has been previously reported that short isoform thymic stromal lymphopoietin (sTSLP) could reduce inflammation in asthmatic airway epithelial cells. Here we wanted to investigate whether the inhibition of sTSLP on asthma is related to aerobic glycolysis. Methods Asthmatic model was established in challenging Male BALB/c mice and 16-HBE (human bronchial epithelial) cell line with house dust mite (HDM). Indicators of glycolysis were assessed to measure whether involve in sTSLP regulating airway epithelial cells inflammation in asthmatic model in vivo and in vitro. Results sTSLP decreased inflammation of asthmatic airway and aerobic glycolysis in mice. HDM or long isoform thymic stromal lymphopoietin (lTSLP) promoted HIF-1α expression and aerobic glycolysis by miR-223 to target and inhibit VHL (von Hippel-Lindau) expression 16-HBE. Inhibition of aerobic glycolysis restrained HDM- and lTSLP-induced inflammatory cytokines production. sTSLP along had almost no potential to alter aerobic glycolysis of 16-HBE. But sTSLP decreased LDHA (lactate dehydrogenase A) and LD (Lactic acid) levels in BALF, and HIF-1α and LDHA protein levels in airway epithelial cells of asthma mice model. lTSLP and sTSLP both induced formation of TSLPR and IL-7R receptor complex, and lTSLP obviously facilitated phosphorylation of JAK1, JAK2 and STAT5, while sTSLP induced a little phosphorylation of JAK1 and STAT5. Conclusion We identified a novel mechanism that lTSLP could promote inflammatory cytokines production by miR-223/VHL/HIF-1α pathway to upregulate aerobic glycolysis in airway epithelial cells in asthma. This pathway is suppressed by sTSLP through occupying binding site of lTSLP in TSLPR and IL-7R receptor complex.

N6-methyladenosine (m6A), the most prevalent form of internal mRNA modification, is extensively involved in Treg cells differentiation and function. However, the involvement of m6A in functional Treg cells for transplantation tolerance remains to be elucidated. By using an experimental transplantation mouse model, we found that m6A levels in Treg cells were altered during the induction of transplant tolerance by performing a dot blotting assay. Subsequently, we used the heterogenic Treg-specific Mettl14 knockout mice (Foxp3-Mettl14f/+ cKO) to reduce METTL14 expression and performed islets allograft transplantation. Our result revealed that reduced expression of METTL14 prevented Treg cells expansion and promoted the infiltration of CD4+ and CD8+ T cells around the allograft, which led to rapid allograft rejection in Foxp3-Mettl14f/+ cKO mice. The expression of regulatory cytokines including IL-10 and TGF-β was significantly decreased in Foxp3-Mettl14f/+ cKO mice, and the suppressive function of Treg cells was also abrogated. In addition, an analysis of RNA-seq data revealed that the SOCS family (SOCS1, SOCS2 and SOCS3) is the subsequent signaling pathway affected by the METTL14 mediated m6A modification in Treg cells to modulate the suppressive function after transplantation. Taken together, our study showed for the first time that the METTL14-mediated m6A modification is essential for the suppressive function of Treg cells in transplantation and may serve as a regulatory element of Treg cell-based therapy in transplant medicine.

BackgroundThe patients undergoing laparoscopic radical colorectomy in many Chinese hospitals do not achieve high compliance with the ERAS (enhanced recovery programs after surgery) protocol.MethodsThe clinical data from 1,258 patients were collected and divided into the non-ERAS and incomplete ERAS groups.ResultsA total of 1,169 patients were screened for inclusion. After propensity score-matched analysis (PSM), 464 pairs of well-matched patients were generated for comparative study. Incomplete ERAS reduced the incidence of postoperative complications (p = 0.002), both mild (6.7% vs. 10.8%, p = 0.008) and severe (3.2% vs. 6.0%, p = 0.008). Statistically, incomplete ERAS reduced indirect surgical complications (27,5.8% vs. 59, 12.7) but not local complications (19,4.1% vs. 19, 4.1%). The subgroup analysis of postoperative complications revealed that all patients benefited from the incomplete ERAS protocol regardless of sex (male, p = 0.037, 11.9% vs. 17.9%; female, p = 0.010, 5.9% vs. 14.8%) or whether neoadjuvant chemotherapy was administered (neoadjuvant chemotherapy, p = 0.015, 7.4% vs. 24.5%; no neoadjuvant chemotherapy, p = 0.018, 10.2% vs. 15.8%). Younger patients (

We present a narrative of the eruptive events culminating in the cataclysmic January 15, 2022 eruption of Hunga Tonga-Hunga Ha'apai Volcano by synthesizing diverse preliminary seismic, volcanological, sound wave, and lightning data available within the first few weeks after the eruption occurred. The first hour of eruptive activity produced fast-propagating tsunami waves, long-period seismic waves, loud audible sound waves, infrasonic waves, exceptionally intense volcanic lightning and an unsteady volcanic plume that transiently reached—at 58 ​km—the Earth's mesosphere. Energetic seismic signals were recorded worldwide and the globally stacked seismogram showed episodic seismic events within the most intense periods of phreatoplinian activity, and they correlated well with the infrasound pressure waveform recorded in Fiji. Gravity wave signals were strong enough to be observed over the entire planet in just the first few hours, with some circling the Earth multiple times subsequently. These large-amplitude, long-wavelength atmospheric disturbances come from the Earth's atmosphere being forced by the magmatic mixture of tephra, melt and gasses emitted by the unsteady but quasi-continuous eruption from 0402±1–1800 UTC on January 15, 2022. Atmospheric forcing lasted much longer than rupturing from large earthquakes recorded on modern instruments, producing a type of shock wave that originated from the interaction between compressed air and ambient (wavy) sea surface. This scenario differs from conventional ideas of earthquake slip, landslides, or caldera collapse-generated tsunami waves because of the enormous (∼1000x) volumetric change due to the supercritical nature of volatiles associated with the hot, volatile-rich phreatoplinian plume. The time series of plume altitude can be translated to volumetric discharge and mass flow rate. For an eruption duration of ∼12 ​h, the eruptive volume and mass are estimated at 1.9 ​km3 and ∼2 900 ​Tg, respectively, corresponding to a VEI of 5–6 for this event. The high frequency and intensity of lightning was enhanced by the production of fine ash due to magma—seawater interaction with concomitant high charge per unit mass and the high pre-eruptive concentration of dissolved volatiles. Analysis of lightning flash frequencies provides a rapid metric for plume activity and eruption magnitude. Many aspects of this eruption await further investigation by multidisciplinary teams. It represents a unique opportunity for fundamental research regarding the complex, non-linear behavior of high energetic volcanic eruptions and attendant phenomena, with critical implications for hazard mitigation, volcano forecasting, and first-response efforts in future disasters.

Sleep deprivation (SD) has become a health problem in the modern society. Although probiotics supplementation has been proven to improve SD-induced gut dysbiosis, the potential neuroendocrine mechanisms remain elusive. In this study, thirty rhesus monkeys (RMs) were recruited. Paradoxical sleep, bright light, and noise were used to build an RM SD model. We examined the plasma γ-aminobutyric acid (GABA), stress hormones, and inflammatory cytokines using ELISAs. 16S ribosomal DNA sequencing and untargeted metabolomics sequencing were employed to detect gut microbial community and metabolites, respectively. The results of our study showed that RMs subjected to SD had elevated plasma stress hormones (such as cortisol and norepinephrine) and proinflammatory cytokines (such as TNF-α, IL-6, and IL-8), and a decreased anti‐inflammatory cytokine IL-10 level. Additionally, SD could give rise to a significant change in gut microbiota and metabolites. The differential gut microbiota and metabolites caused by SD were enriched in the signaling pathways related to GABA metabolism. Pearson correlation analysis revealed that there is a significant correlation between plasma GABA and SD-induced stress responses and gut dysbiosis. The supplementation of GABA-producing probiotics could significantly increase the relative abundance of Lactobacillus and plasma GABA levels, and reverse SD‐induced stress responses and gut dysbiosis. Therefore, we speculated that SD-induced stress response and gut dysbiosis might be an outcome of reduced gut-derived GABA absorption. The supplementation of GABA-producing Lactobacillus might be beneficial for the treatment of SD-induced intestinal dysfunction.

Abstract Background Transmembrane 4 L six family member 1 (TM4SF1) is upregulated in several epithelial cancers and is closely associated with poor prognosis. However, the role of TM4SF1 and its potential mechanism in colorectal cancer (CRC) remain elusive. Methods We investigated the expression of TM4SF1 in the Oncomine, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of CRC tissues. The effect of TM4SF1 on the epithelial-to-mesenchymal transition (EMT) and cancer stemness of CRC cells was investigated by Transwell, wound healing and sphere formation assays. A series of in vitro and in vivo experiments were conducted to reveal the mechanisms by which TM4SF1 modulates EMT and cancer stemness in CRC. Results TM4SF1 expression was markedly higher in CRC tissues than in non-tumour tissues and was positively correlated with poor prognosis. Downregulation of TM4SF1 inhibited the migration, invasion and tumour sphere formation of SW480 and LoVo cells. Conversely, TM4SF1 overexpression significantly enhanced the migration, invasion and tumoursphere formation potential of CRC cells, Additionally, TM4SF1 silencing inhibited the EMT mediated by transforming growth factor-β1 (TGF-β1). Mechanistically, gene set enrichment analysis (GSEA) predicted that the Wnt signalling pathway was one of the most impaired pathways in TM4SF1-deficient CRC cells compared to controls. The results were further validated by WB, which revealed that TM4SF1 modulated SOX2 expression in a Wnt/β-catenin activation-dependent manner. Furthermore, we found that knockdown of TM4SF1 suppressed the expression of c-Myc, leading to decreased c-Myc binding to the SOX2 gene promoter. Finally, depletion of TM4SF1 inhibited metastasis and tumour growth in a xenograft mouse model. Conclusion Our study substantiates a novel mechanism by which TM4SF1 maintains cancer cell stemness and EMT via the Wnt/β-catenin/c-Myc/SOX2 axis during the recurrence and metastasis of CRC.

Existing image generation models have achieved the synthesis of reasonable individuals and complex but low-resolution images. Directly from complicated text to high-resolution image generation still remains a challenge. To this end, we propose the instance mask embedding and attribute-adaptive generative adversarial network (IMEAA-GAN). Firstly, we use the box regression network to compute a global layout containing the class labels and locations for each instance. Then the global generator encodes the layout, combines the whole text embedding and noise to preliminarily generate a low-resolution image; the instance embedding mechanism is used firstly to guide local refinement generators obtain fine-grained local features and generate a more realistic image. Finally, in order to synthesize the exact visual attributes, we introduce the multi-scale attribute-adaptive discriminator, which provides local refinement generators with the specific training signals to explicitly generate instance-level features. Extensive experiments based on the MS-COCO dataset and the Caltech-UCSD Birds-200-2011 dataset show that our model can obtain globally consistent attributes and generate complex images with local texture details.

Avasimibe (Ava) is an acetyl-CoA acetyltransferase 1 (ACAT1) specific inhibitor and an established medicine for atherosclerosis, owing to its excellent and safe anti-inflammation effects in humans. However, its efficacy in asthma has not yet been reported. We first administered varying concentrations of avasimibe to house dust mite (HDM)-induced asthmatic mice; results showed that 20 mg/kg avasimibe most significantly reduced IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF) and total IgE in serum, and the avasimibe treatment also exhibited lower mucus secretion, decreased goblet and basal cells but increased ciliated cells compared to the HDM group. And the redistribution of adherens junction (AJ) proteins induced by HDM was far more less upon avasimibe administration. However, avasimibe did not reduce the cholesterol ester ratio in lung tissues or intracellular cholesterol ester, which is avasimibe’s main effect. Further analysis confirmed that avasimibe impaired epithelial basal cell proliferation independent of regulating cholesterol metabolism and we analyzed datasets using the Gene Expression Omnibus (GEO) database and then found that the KRT5 gene (basal cell marker) expression is correlated with the β-catenin gene. Moreover, we found that β-catenin localized in cytomembrane upon avasimibe treatment. Avasimibe also reduced β-catenin phosphorylation in the cytoplasm and inactivated the Wnt/β-catenin signaling pathway induced by HDMs, thereby alleviating the airway epithelial barrier disruption. Taken together, these findings indicated that avasimibe has potential as a new therapeutic option for allergic asthma.

Herein, epoxy resins for composite liquid oxygen (LOX) fuel tanks are modified with phosphorous flame retardant (DOPO) and brominated epoxy resin (EX48). With the incorporation of DOPO and EX48, the processing properties requirements for the hot-melt prepreg are contented with the significantly enhanced viscosity of the modified epoxy resin. At the same time, the tensile performance, flexural performance and fracture toughness of epoxy resin at room temperature and 90 K are improved with the introduction of DOPO and EX48. In addition, the epoxy resin of EP/P7.7/Br40 offers a highest limited oxygen index of 33.5% and a lowest LOX impact sensitivity of 5% with the eliminated LOX incompatible reactions including explosion and combustion. Consideration of the excellent cryogenic mechanical properties and LOX compatibility, combined with ideal viscosity for hot-melt prepreg preparation, the epoxy resin modified with DOPO and EX48 simultaneously is attractive as the polymer matrix for composite LOX fuel tanks.

Background: Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown. Methods: A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients. Findings: Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme. Interpretation: The models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.

ATC (air traffic control) automation system is a complex system, which helps maintain the air traffic order, guarantee the flight interval, and prevent aircraft collision. It is essential to ensure the safety of air traffic. Failure effects evaluation is an important part of ATC automation system reliability engineering. The failure effects evaluation of ATC automation system is aimed at the effects of modules or components which affect the performance and functionality of the system. By analyzing and evaluating the failure modes and their causes and effects, some reasonable improvement measures and preventive maintenance plans can be established. In this paper, the failure effects evaluation framework considering performance and functionality of the system is established on the basis of reliability theory. Some algorithms for the quantitative evaluation of failure effects on performance of ATC automation system are proposed. According to the algorithms, the quantitative evaluation of reliability, availability, maintainability, and other assessment indicators can be calculated.

One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant methylation of the promoter. However, the relationship between DAPK1 methylation and the risk of gastrointestinal cancer is still controversial. Hence, we conducted this study to determine the potential correlation.Eligible publications were searched in the Pubmed, Embase, and Cochrane Library through November 2016 according to the inclusion criteria and exclusion criteria. Revman 5.3 and Stata 12.0 software were used to analyze the relevant data regarding the association between the frequency of DAPK1 methylation and gastrointestinal cancer.A total of 22 studies with 2406 patients were included in this meta analysis. Methylation of DAPK1 was positively related with the risk of gastrointestinal cancer (odds ratio [OR] = 5.35, 95% confidence interval [CI]: 2.76-10.38, P

The strain transfer characteristics of resistance strain gauge are theoretically investigated. A resistance strain-type transducer is modeled to be a four-layer and two-glue (FLTG) structure model, which comprises successively the surface of an elastomer sensitive element, a ground adhesive glue, a film substrate layer, an upper adhesive glue, a sensitive grids layer, and a polymer cover. The FLTG model is studied in elastic–mechanical shear lag theory, and the strain transfer progress in a resistance strain-type transducer is described. The strain transitional zone (STZ) is defined and the strain transfer ratio (STR) of the FLTG structure is formulated. The dependences of the STR and STZ on both the dimensional sizes of the adhesive glue and structural parameters are calculated. The results indicate that the width, thickness and shear modulus of the ground adhesive glue have a greater influence on the STZ ratio. To ensure that the resistance strain gauge has excellent strain transfer performance and low hysteresis, it is recommended that the paste thickness should be strictly controlled, and the STZ ratio should be less than 10%. Moreover, the STR strongly depends on the length and width of the sensitive grids.

This paper provides a method to determine the variable flexible joint parameters which are dependent on configurations for a PRS Parallel Robot. Based on the continuous force approach, virtual springs were used between the joint components to simulate the joint flexibility. The stiffness matrix of the joint virtual springs was derived. The method uses system dynamic characteristics in different configurations to set the virtual spring stiffness for all the joints in the system. Modal testing was conducted on a set of selected robot configurations to determine the system natural frequencies and mode shapes along with their variation. To obtain the virtual spring stiffness, the system was condensed at the joint nodal coordinates. Then eigen-sensitivity analysis was conducted on the condensed system matrices with respect to the stiffness parameters of the joint virtual springs. Thus, the virtual spring parameters in the model can be set to match the variation of the system dynamic responses with the robot configuration changes. The virtual spring parameters between the selected robot configurations were obtained by interpolation. The research indicates that the method is effective and relatively easy to conduct, compared to other methods. The variable flexible joint model is applicable to flexible multibody systems with variable configurations.

Objective: Insomnia is a common symptom in subhealthy states. In patients, long-term insomnia symptoms can lead to decreased immune function, even mental depression, thus seriously affecting quality of life. Therefore, this study aims to observe the therapeutic effect of huo li su (HLS) oral solution combined with zopiclone in the treatment of insomnia to find suitable drugs for treatment. Methods: A total of 161 patients with insomnia from January 2017 to March 2022 were selected in this retrospective cohort study. The patients were divided into the observation (82 cases, receiving HLS oral solution and zopiclone) and control (79 cases, receiving zopiclone alone) groups in accordance with therapeutic drug administration. The differences in the scores of the 2 groups on the Sleep Disorder Scale (SDRS), Pittsburgh Sleep Quality Index (PSQI), Fatigue Inventory 14 (FS-14), and traditional Chinese medicine (TCM) syndromes before and after treatment were compared. Results: No significant differences in age, gender, disease duration, body mass index (BMI), and other general data were found between the 2 groups (P > .05). The TCM syndrome, PSQI, FS-14, and SDRS scores before treatment of the 2 groups were not significantly different (P < .05). After 4 weeks of treatment, the TCM syndrome, PSQI, FS-14, and SDRS scores of the observation group were significantly lower than those of the control group. Conclusion: HLS oral solution combined with zopiclone can effectively improve insomnia symptoms and is superior to zopiclone alone. [ABSTRACT FROM AUTHOR]